Background: Lung-MAP (S1400) is a master umbrella protocol designed to establish genomic screening for previously treated squamous cell lung cancer patients (SqCCA), and independently evaluate targeted therapies with matching biomarkers and alternative therapies (designated non-match therapy) in patients without putative markers. The protocol opened June 16, 2014 with four biomarker-driven sub-studies and one non-match sub-study.

Method: Eligibility stipulated advanced SqCCA, progressing after at least one prior platinum-based chemotherapy, PS 0–2, and EGFR/ALK wild-type. Tumor samples were required and analyzed for gene alterations by FoundationOne NGS assay (Foundation Medicine). The original biomarker and non-match studies were: S1400B evaluating taselisib for PI3K mutations, S1400C evaluating palbociclib for cell cycle gene alterations (CCGA), S1400D evaluating AZD4547 for FGFR mutations, S1400E evaluating rilotumumab and erlotinib for c-MET positive tumors, and S1400A evaluating durvalumab in patients with no matching biomarkers. The original design included randomization to a control arm, but was amended to a single-arm phase 2 design. The primary endpoint for each modified sub-study was response.

Result: As of June 16, 2017 all original sub-studies have been closed to accrual; 1298 patients registered to the screening component of the trial and 486 patients have registered to a sub-study. Two new sub-studies have been launched and are currently accruing. Details of the completed sub-studies are included in the table.

Sub-study

Final Accrual

Biomarker prevalence/% of sub-study registrations

Closure Date

Response to investigational therapy N (%)

Status

S1400A (non-match)

Total: 116 Durvalumab: 78 Docetaxel: 38

NA/59%

12/18/15 Docetaxel arm closed: 4/22/15

11 (16%)

Administratively closed to enable activation of new non-match study.

S1400B PI3K

Total: 39 taselisib: 31 Docetaxel: 8

8%/9%

12/12/16 Docetaxel arm closed: 12/18/15

1 (4%)

Closed at interim futility analysis.

S1400C (CCGA+)

Total: 54 Palbociclib: 37 Docetaxel: 17

19%/15%

09/01/16 Docetaxel arm closed: 12/18/15

2 (6%)

Closed at interim futility analysis.

S1400D (FGFR+)

Total: 45 AZD4547: 35 Docetaxel: 10

16%/12%

10/31/16 Docetaxel arm closed: 12/18/15

2 (7%)

Closed at interim futility analysis.

S1400E (MET+)

Total: 9 R+E: 4 E: 5

N/A (closed too early)

11/26/2014

N/A

Closed d/t discontinuation of development of rilotumumab

Conclusion: Lung-MAP as a master genomic screening protocol has demonstrated feasibility with respect to accrual and evaluation of targeted therapies in lower prevalence patient populations. This dynamic, centralized, single-IRB platform is well positioned to efficiently assess multiple novel therapeutics for advanced SqCCA patients.

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